A chromosomal inversion has been identified in a region of chromosome 18 that has recently been shown to contain a very significant locus for developmental dyslexia. It is hypothesized that one of the breakpoints of this chromosomal inversion disrupts a gene influencing language ability. The same gene leading to the defect in this family could underlie the mutational basis of developmental dyslexia. The following aims will be accomplished: 1) Map the inversion breakpoints, 2) Identify the candidate gene(s), and 3) Screen for mutations in this gene in an independent sample. Fluorescence in situ hybridization (FISH) and Southern blotting analysis will be used to locate the breakpoints. The gene at or near this disruption will then be screened for mutations, by sequencing analysis, in samples showing linkage to this region. Mapping genes by finding the breakpoints of chromosomal anomalies gives one a considerable advantage because often the gene at the site of disruption is the disease susceptibility gene. By identifying a disrupted gene in our samples with inherited dyslexia, and screening for a mutation in linked samples, this project aims to circumvent years of work and identify a gene causing susceptibility to developmental language disorders. This information will be invaluable in aiding to elucidate the mechanisms underlying neurodevelopmental disorders involving language.